Chiral bisphosphinites are well-documented alternatives for chiral bisphosphines as ligands that can be exploited in various asymmpetric syntheses. Particularly, vicinal biarylphophinite ligands give a seven membered chelate ring similar to the successful DIOP on coordination to the metal. RajanBabu and coworkers have described asymmetric bisphosphinites obtained by functionalization of sugars and have shown their utility in enantioselective hydrogenation, hydrovinylation and hydrocynation reactions. Despite the interesting reactions demonstrated by bisphosphinites, not much attention has been paid to their synthesis and catalysis. This is probably due to the known moisture and oxygen sensitivity that makes their use limited. In the present thesis, a series of C1 an C2 symmetric bisphosphinite complexes of Pd(II) and Pt(II) have been synthesized directly from various naturally occurring chiral alcohols using a modified template method. A number of asymmetric catalytic reactions have been developed such as allylation of imines, allylation of aldehydes, allylic allylation, allylic alkylation, hydrosilylation of alkenes and regioselective allylation of oxiranes. Allylation of imines was carried out in essentially neutral conditions using Pd(II) catalysts and water was shown to accelerate the reaction. Interestingly acetic acid was required as a promoter in asymmetric allylation of cinnamaldehyde in the Pt(II) catalyzed reaction whereas water was a deterrent. Hydrosilylation reaction was carried out in solvent free conditions with high turnover numbers (.1000). Ascorbic acid based complexes produced the highest enantioselectivity for the asymmetric allylic alkylation reaction (97 % ee) and hydrosilylation of styrene (98% ee). These enantioselectivity results are the best obtained using ligands directly prepared from natural products.

<p>This thesis deals with the design and syntheses of chiral,enantiopure pyridinecontaining ligands and their applicationsin asymmetric catalyis.</p><p>Chiral pyridyl pyrrolidine ligands and pyridyl oxazolineligands were synthesized and employed in thepalladium-catalysed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate. Theinfluence of the steric properties of the ligands wereinvestigated.</p><p>Ditopic ligands, containing crown ether units as structuralelements, were synthesized and some of the ligands were used asligands in the palladiumcatalysed allylic alkylation of1,3-diphenyl-2-propenyl acetate with dimethyl malonate. A smallrate enhancement was observed, compared with analogous ligandslacking the crown ether unit, when these ditopic ligands wereused in dilute systems.</p><p>A modular approach was used to synthesize chiralenantiomerically pure pyridyl alcohols and C2-symmetric2,2’-bipyridines, with the chirality originating from thechiral pool. Electronic and steric properties of the compoundswere varied and they were used as ligands in theenantioselective addition of diethylzinc to benzaldehyde. Thesense of asymmetric induction was found to be determined by theabsolute configuration of the carbinol carbon atom. Theelectronic properties of the ligands had a minor influence onthe levels of enantioselectivity induced by the ligands.</p><p>Chiral pyridyl phosphinite ligands and pyridyl phosphiteligands were synthesized from the pyridyl alcohols andevaluated as ligands in palladiumcatalysed allylic alkylations.With the phosphinite ligands, the sense of chiral induction wasfound to be determined by the absolute configuration of theformer carbinol carbon atom. A kinetic resolution of theracemic starting material was observed with one of thephosphite ligands. Moderate enantioselectivities wereachieved.</p><p><b>Kewords:</b>asymmetric catalysis, chiral ligand, chiralpool, oxazoline, crownether, ditopic receptor, bipyridine,pyridyl alcohol, modular approach, P,Nligand, diethylzinc,allylic alkylation.</p>

The thesis entitled “Organocatalytic Cascade Cyclizations for the Enantioselective Synthesis of Spirooxindoles” is divided into three chapters. Chapter 1: Catalytic Enantioselective Michael Addition/Cyclization Cascade of 3-Isothiocyanato Oxindoles with Nitroolefins A myriad of spirocyclic frameworks present in natural product, and pharmaceutically important compounds, has attracted the synthetic organic chemists to explore their preparation in enantioselective manner. Consequently various strategies have been devised for efficiently accessing highly functionalized spirooxindoles. Among these strategies, the use of 3-isothiocyanato oxindoles as the building block appeared as the most popular one. The combination of 3-isothiocyanato oxindoles and a variety of electrophiles have already been reported. However one of the most popular electrophiles, nitroolefins, has never been used in the reaction with 3-isothiocyanato oxindoles. In this chapter, a highly efficient catalytic asymmetric Michael addition/cyclization cascade reaction between 3-isothiocyanato oxindoles and β-substituted nitroolefins with the help of a cinchonidine-derived bifunctional thiourea catalyst has been discussed. Highly functionalized spirooxindoles containing three successive stereocenters were obtained in high yield with moderate to good diastereo- and enantioselectivity. Reference: Kayal, S.; Mukherjee, S. Eur. J. Org. Chem. 2014, 6696-6700. Chapter 2: Catalytic Aldol-Cyclization Cascade of 3-Isothiocyanato Oxindoles with α-Ketophosphonates for the Enantioselective Synthesis of β-Amino-α-Hydroxyphosphonates The oxindole scaffold containing a quaternary stereocenter at the C3 position is a privileged structural motif present in many biologically active molecules and natural products. In this respect, spirooxindoles have received special attention during the past few years. Similarly, β-Amino and/or hydroxy functionalized phosphonic acids and their derivatives are found to display inhibitory activities towards a range of enzymes such as renin, HIV protease, thrombin, and various classes of protein tyrosine kinases and phosphatases. Considering the importance of both oxindole and β-amino-α-hydroxyphosphonic acid, we reasoned that highly functionalized phosphonic acid derivatives based on a spirooxindole framework could be of potential biological significance, if synthesized in enantiopure form This chapter deals with a cascade aldol-cyclization reaction between 3-isothiocyanato oxindoles and α-ketophosphonates for the enantioselective synthesis of spirooxindole-based β-amino-α-hydroxyphosphonate derivatives. Catalyzed by cinchona alkaloid-based bifunctional thiourea derivatives, this protocol delivers 2-thioxooxazolidinyl phosphonates bearing two adjacent quaternary stereogenic centers, generally in high yields with excellent diastereo- and enantioselectivities. Both the product enantiomers are accessible with nearly equally high level of enantioselectivity. Reference: Kayal, S.; Mukherjee, S. Org. Lett. 2015, 17, 5508-5511. Chapter 3: Catalytic Michael Addition/Cyclization Cascade of 3-Isothiocyanato Oxindoles with Cyclic α,β-Unsaturated Ketones: A Concise Enantioselective Synthesis of Bispiro[indoline-3,2'-pyrrolidine] Among different spirocyclic cores, the spirooxindole framework containing pyrrolidinyl ring represents a very important class owing to their biological activities such as antimicrobial, anticancer, antihypertensive, antidiabetic, antimycobacterial and antitubercular properties. Similarly, the bispirooxindole scaffold recently has drawn considerable interests because of its exclusive structural and stereochemical diversity. Only a few examples have been reported till date for enantioselective construction of the pharmaceutically important bispirooxindole architectures. Considering the importance of bispirooxindoles and pyrrolidinyl spirooxindole scaffolds, we were interested in merging them in a single molecular framework. In this chapter, a Michael addition/cyclization cascade reaction between 3-isothiocyanato oxindoles and exocyclic enones for the enantioselective synthesis of 3,2′-pyrrolidinyl bispirooxindole derivatives has been illustrated. With the help of a quinine-derived bifunctional squaramide as the catalyst, this protocol delivers bispirooxindoles bearing three contiguous stereogenic centers, in high yields and generally with outstanding diastereo- and enantioselectivity. Reference: Kayal, S.; Mukherjee, S. manuscript under preparation.

Dans cette thèse les résultats dans le domaine de la synthèse des dérivée des TADDOL et leur capacité d’induction chirale sont présentés. Une librairie des TADDOLs a été synthétisée et une analyse conformationnelle par VCD a été faite. Ces composés enantiopurs ont été testés dans la réaction de cyanosilylation enantioselective en donnant des résultats moyens. En partant de TADDOL nous avons synthétisé des dérivée phosphorés, des amines et des (thio)urées. Les dérivés de P(III) ont été utilisés comme ligands pour le palladium dans l’alkylation allylique asymétrique et les amines dans le réarrangement des époxydes meso. Les (thio)urées ont été testées pour leur capacité de complexation des anions carboxylates. / In this thesis are presented the results in the field of synthesis of TADDOL derivatives and their chiral induction capacity. A family of TADDOLs was synthesized and a conformational analysis was performed by VCD. These enantipure compounds were tested in enantioselective cyanosilylation reactions obtaining moderate results. Starting from TADDOL we obtained phosphorus derivatives, amines and (thio)ureas. The P(III) derivatives were tested as ligands for palladium in asymmetric allylic alkylation and the amines in the rearrangement of meso-epoxides. The (thio)ureas were screened for complexation capacity for carboxylate anions.

6 Title: Sythesis and catalytic properties of ferrocenophane phosphines Author: Karel Škoch Institution: Faculty of Science, Charles University in Prague, Department of Inorganic Chemistry Supervisor: prof. RNDr. Petr Štěpnička, Ph.D. Keywords: ferrocene, ferrocenophane, phosphine ligands, palladium, asymetric catalysis, aza- Morita-Baylis-Hillman reaction, asymetric allylic alkylation Abstract: This Thesis describes the preparation of five sterically and electronically different ferrocene phosphines, (R)-1,1'-[1-(diarylphosphino)propan-1,3-diyl]ferrocenes (R)-1a-e, and a study into their coordination and catalytic properties. The key precursor of the phosphine synthesis, chiral alcohol (R)-2, was prepared according to the procedure described in the literature. Alcohol (R)-2 was converted with retention of configuration to diarylphosphines (R)-1a-e in one-step reaction with trimethylsilylchloride and sodium iodide and then with the corresponding diarylphosphine. Phosphines 1a-e were characterized by NMR and MS methods. For the basic representative 1a the following palladium(II) complexes were prepared: [PdCl(LNC )(1a)] (10, LNC = 2-[(dimethylamino)methyl]phenyl-C1 ,N) and trans- [PdCl2(1a)2] (9a). In addition, the isomeric complex cis-[PdCl2(1a)2] (9b) was isolated from the reaction mixture after catalytic...

The topic of this thesis is the design and synthesis of biaryl-based self adaptableligands for asymmetric metal catalysis. The results discussed in papers I-III are covered, together with some unpublished results concerning substrate-adaptable catalysts. A general survey of self-adaptable catalysts is presented first. The second chapter of this thesis starts with a survey of inversion barriers in biphenyl-based ligands and catalysts. Thereafter, the determination of barriers to conformational adaptation in dibenzoazepines and dibenzophosphepines is described. Palladium complexes with a diphosphine ligand or a diamine ligand, as well as the free diamine ligand, were studied. Entropies and enthalpies of activation were determined with variable temperature NMR spectroscopy. The mechanism of conformational change in the metal complexes was elucidated. The third chapter describes the synthesis of semiflexible and rigid phosphinite ligands, as well as their application in rhodium-catalysed asymmetric hydrogenation. Modest enantioselectivities (up to 63% ee) were obtained. The semiflexible ligand was found to behave like the most active rigid diastereomer. The fourth chapter describes the behaviour of amine and phosphoramidite ligands in model complexes relevant to the palladium-catalysed asymmetricallylic alkylation of benchmark substrates. Diphosphoramidite and aminephosphoramiditeligands were designed and synthesised. Pd(olefin) complexesof diamine and diphosphoramidite ligands were studied, and their symmetry determined. It was found that both types of ligands are able to adapt their conformation to the substrate. / QC20100630

This thesis deals with the design and synthesis of ligands for asymmetric catalysis: palladium catalyzed allylic alkylations, and rho-dium and iridium catalyzed hydrogenations of olefins. Chirally flexible phosphepine ligands based on biphenyl were synthesized and their properties were studied. The rotation barrier for configurationally flexible phosphepines was determined by NMR spectroscopy. The ratio of the atropisomers was shown to depend on the group bound to phosphorus. Only complexes with two homochiral ligands bound to the metal center were observed upon complexation with Rh(I). It was shown that one diastereomer of the flexible ligand exhibits higher activity but lower selectivity than its diastereomer in the rhodium catalyzed hydrogenation of methyl alfa-acetamidocinnamate. These ligands were also tested in nickel catalyzed silabora-tions. Chiral P,N-ligands with pseudo-C2 and pseudo-CS symmetry based on pyrrolidines-phospholanes or azepines-phosphepines were synthesized and studied in palladium catalyzed allylic alkylations. Semi-flexible azepine-phosphepine based ligands were prepared and their ability to adopt pseudo-C2 or pseudo-CS symmetry depending on the substrate in allylic alkylations was studied. It was shown on model allyl systems with flexible N,N-ligands that the ligand prefers CS-symmetry in compexes with anti-anti as well as syn-syn allyl moieties, but that for the latter type of complexes, according to computations, the configuration of the ligand is R*,R* in the olefin complexes formed after addition of a nucleophile to the allylic group. A preliminary investigation of the possibilities to use a su-pramolecular approach for the preparation of P,N-ligands with pseudo-C2 and pseudo-S symmetry was made. An N,N-ligand with C2 symmetry was prepared and its activity in palladium catalyzed ally-lic alkylation was studied. Pyridine-based P,N-ligands were tested in iridium catalyzed hy-drogenations of unfunctionalized olefins with good activities and se-lectivities. In order to attempt to improve the selectivity, ligands with a chirally flexible phosphepine fragment were prepared and applied in catalysis with promising results. / QC 20100929

Plusieurs ligands dérivés de la D-glucosamine, conçus pour différentes réactions catalytiques,ont été synthétisés. Les ligands pour la catalyse homogène basés sur 1,2-glucodiamine ontété préparés, et utilisés dans des réactions d'alkylation allylique, d'hydrogénation et d'additionde Michael.La D-glucosamine a utilisee pour la preparation de catalysateur type de SPAC (SupportedAqueous Phase Catalyst). Ce catalysateur hétérogène été utilisé avec de très bons résultatsdans les réactions de couplage croisé de Suzuki Miyaura. Le catalyseur a également étérecyclé. Des essais de préparation de ligands greffés sur une matrice de silice de type SBA-15ont été réalisés ainsi que des ligands à base de poly (éthylène) glycol. / Several ligands derived from D-glucosamine, designed for different catalytic reactions havebeen synthesized. The ligands for homogeneous catalysis based on 1,2-glucodiamine wereprepared, and used in reactions of allylic alkylation, hydrogenation and Michael addition.Supported Aqueous Phase Catalyst (SAPC) system was prepared from D-glucosamine anduse with very good results in Suzuki Miyaura cross coupling reactions. Catalyst was alsorecycled. Attempt to prepare ligands grafted on SBA-silica matrix were made as well asligands containing poly(ethylene) glycol moiety.